2022 Fiscal Year Final Research Report
Significance of reduced alphaGlcNAc glycosylation in pyloric gland neoplasms
| Project/Area Number |
19K16555
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 幽門腺型 / MUC6 / 糖鎖修飾 / 多段階発がん / 前がん / 腫瘍マーカー / 胃型形質 / 粘液 |
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| Outline of Final Research Achievements |
Gstric gland mucin consists core protein MUC6 with
α1,4-N-acetylglucosamine (αGlcNAc) glycosylation. Mice deficient
in αGlcNAc develop gastric adenocarcinoma. In human, αGlcNAc glycosylation was frequently lost in adenocarcinoma expressing gastric mucin. We have studied MUC6 and αGlcNAc expression in malignant and pre-malignant lesions with gastric mucin expression in extra-gastric organs. In all organs, decreased αGlcNAc-glycosylation on MUC6 was frequently observed in not only malignant but pre-malignant lesions. Furthermore, in uterine cervix, patients with αGlcNAc negative adenocarcinoma had poor prognosis. In lung, those with MUC6 negative adenocarcinoma had poor prognosis. Furthermore we studied MUC6 and αGlcNAc effect in cancer cell line models. Ectopic MUC6 expression attenuated cancer malignancy, and αGlcNAc glycosylation enhanced its phenotypes. These results show that phenotypic change of mucin is a malignant biomarker in various organ neoplasms with gastric mucin.
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| Free Research Field |
病理学
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| Academic Significance and Societal Importance of the Research Achievements |
幽門腺型粘液の産生を伴う腫瘍は、諸臓器においてみられるが、しばしば、組織学的に、細胞異型に乏しい症例が存在する。ゆえに、病理診断の現場において、その早期病変の診断が難しい場合がある。本研究によって、早期病変マーカーとしてαGlcNAcの低下・消失が明らかになったことで、幽門腺型粘液の産生を伴う腫瘍の早期診断の大きな一助になると考えられる。また、ヒトがん由来培養細胞株を用いた実験により、MUC6の発現、αGlcNAcの糖鎖修飾低下が、直接、がん細胞の悪性化にかかわることが明らかになった。今後その機序をさらに明らかにすることで、これらの腫瘍に対する、新たな分子標的療法が可能になると考えられる。
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